Cloning and analysis of a FoxO transcription factor from Xiphophorus

Melanoma development in the fish Xiphophorus is determined, at least in part, by overexpression and activation of the Xmrk-2 oncogene, which triggers a variety of signal transduction pathways resulting in altered cell cycle control. We have begun analysing transcription factors which may link Xmrk-2...

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Veröffentlicht in:Gene 2003-01, Vol.302 (1), p.31-41
Hauptverfasser: Rudd, Michael D., Johnston, Dennis A., Kazianis, Steven, Butler, Andrew P.
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Johnston, Dennis A.
Kazianis, Steven
Butler, Andrew P.
description Melanoma development in the fish Xiphophorus is determined, at least in part, by overexpression and activation of the Xmrk-2 oncogene, which triggers a variety of signal transduction pathways resulting in altered cell cycle control. We have begun analysing transcription factors which may link Xmrk-2 with regulation of cell proliferation or apoptosis. Towards this end, we have cloned an FKHR (FoxO sub-family) homolog from Xiphophorus maculatus. The isolated clone is a 2.7 kb cDNA encoding a predicted protein of 664 amino acids. The gene, which we have named FoxO5, maps to Xiphophorus Linkage Group XV. The protein product can be categorized within a branch of the FOXO sub-class, which includes: Danio rerio zFKHR (foxo5), Homo sapiens FKHR-L1 (FoxO3a) and Mus musculus FKHR2 (Foxo3). Notably, the Forkhead DNA binding domain, three Akt consensus phosphorylation sites and a carboxy-terminal minimal activation domain are each highly conserved. A mutated FoxO5 protein with disrupted Akt phosphorylation sites inhibits proliferation, but the wild-type protein fails to do so, when exogenously expressed in Xiphophorus cells derived from a melanoma. The same mutated protein predominantly localizes to the nucleus, yet the wild-type protein seldom does. Further characterization of Xiphophorus FoxO5 will contribute to understanding the molecular basis of carcinogenesis in these species.
doi_str_mv 10.1016/S0378-1119(02)01100-9
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ispartof Gene, 2003-01, Vol.302 (1), p.31-41
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language eng
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source MEDLINE; Elsevier ScienceDirect Journals
subjects Animal model
Animals
Base Sequence
Chromosome Mapping
Cloning, Molecular
Cyprinodontiformes - genetics
Cytoplasm - metabolism
DNA, Complementary - chemistry
DNA, Complementary - genetics
DNA, Complementary - isolation & purification
Female
Forkhead
FoxO5
FoxO5 gene
Freshwater
Gene Expression
Genetic map
Green Fluorescent Proteins
Luminescent Proteins - genetics
Luminescent Proteins - metabolism
Male
Molecular Sequence Data
Phylogeny
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Sequence Analysis, DNA
Sequence Homology, Amino Acid
Transcription Factors - genetics
Tumor Cells, Cultured
Xiphophorus maculatus
Xmrk-2 gene
title Cloning and analysis of a FoxO transcription factor from Xiphophorus
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